Cerebral Cortex Structure Changes And Their Correlation With Cognitive Function In Lung Cancer Patients

doi:10.21203/rs.3.rs-1401186/v1

To assess differences in cerebral cortex structure changes between lung cancer and healthy controls, and to analyze their correlation with cognitive function. 33 patients diagonosed with primary lung cancer have been enrolled in a prospective study. Before starting treatment and 2-4 months after recieving treatment, the patients underwent assessment of cognitive function, and activities of daily living, as well as a T1-weighted magnetic resonance imaging. The patients were compaired with 33 sex, age and education-matched healthy controls. Neuropsychological assessment, MoCA and Tail Making Test (TMT), shows that 78.8% of newly diagnosed lung cancer patients had mild to moderate cognitive impairment. patients' visual space and executive ability deteriorated after treatment (t=2.66, d=0.66, P=0.02). At baseline, some cerebral cortex of frontal, temporal and parietal lobes were atrophied, especially anterior central gyrus, rostral middle frontal cortex, superior temporal gyrus, middle temporal gyrus and temporal pole. After treatment, the rostral middle frontal cortex of the right brain was further atrophied (P＜0.005). There was a positively correlation between atrophied cortical thickness in newly diagnosed lung cancer patients and the score of part A of TMT. Temporal pole volume was positively correlated with naming (r=0.39, P=0.03) and language (r=0.43, P=0.02), while middle temporal gyrus was positively correlated with attention (r=0.39, P=0.03) and orientation (r=0.39, P=0.04). In summary, this study suggests that cancer itself and treatment lead to cognitive impairment, as well as cortical thickness and volume reduction, and cerebral cortex structure changes are correlated with cognitive function. Confirming the existence of cancer-related cognitive impairment and cancer-related brain injury.

Lung cancer

Cognitive function

Cancer-related cognitive impairment

Magnetic resonance imaging

Lung cancer accounts for 11.6% of the global cancer incidence and 18.4% of all cancer deaths¹. The high morbidity and mortality of lung cancer promotes the advancement of lung cancer screening and treatment. With the early screening and detection of cancer, precise staging, timely interventions and effective treatment, the 5-year survival rate of the lung cancer population has increased from 15.6% in 2011 to 19.4% in 2019¹. The prolonged survival means that attention to lung cancer populations is not only to prolong the survival time, but also to improve their quality of life.

In 1980s, chemotherapy was considered as the major variable associated with cognitive impairment in cancer patients². After 1990, the scientifc literature have shown that chemotherapy^{3, 4}, radiotherapy⁵, hormone therapy⁶, targeted therapy^{7, 8} or even immunotherapy⁹ may also contribute to lower cognitive performance in cancer patients and survivors. Since the 20th century, the tumor itself was also confirmed to affect cognitive function and brain structure^10,11,12. Cancer-related cognitive impairment (CRCI) refers to the cognitive dysfunction and the functional structure impaired of the patient’s brain caused by cancer¹³, it often presented with mild to moderate cognitive impairment¹⁴, mainly manifested in decreased memory, visuospatial and verbal fluency abilities^15,16. Executive functioning and processing/psychomotor speed are also commomly affected domains¹⁷. CRCI may affect up to 78% of cancer survivors and affect their quality of life¹⁸. 17–34% of cancer patients have long-term cognitive impairment¹⁴, and some patients have cognitive impairment that can last for 20 years¹⁹.

In recent decades, some studies incorporated neuroimaging technology to explore concomitant structural and functional brain abnormalities. An structural neuroimaging research in breast cancer patients found that microstructural abnormalities of some certain vulnerable white matter regions after chemotherapy²⁰. And some literatures used neuroimaging technology to explore the correlation between brain structure and functional imaging and cognitive impairment^{21, 22, 23}, trying to clarify the underlying mechanism of CRCI. So far, most of the relationship between neuroanatomy and cognitive function come from studies on breast cancer patients^{15, 24}, although there are reports of CRCI for lung cancer populations^{10, 16}, it is much less than breast cancer and results are inconsistent. Owing to the poor overall prognosis of lung cancer and the difficulty in follow-up, and there are short of longitudinal examination of whole-brain or regional structural diferences for lung cancer populations, research on the short-term or long-term effects of brain and cognition remains challenging.

For brain diseases, T1-weighted MRI is cheaper than functional MRI, blood oxygen level dependence (BOLD) or positron emission tomography/computed tomography (PET/CT), and it’s the most commonly used and simplest detection method in clinical practice. Meanwhile, T1-weighted MRI has the advantages of high-resolution anatomical images, good contrast between white matter and gray matter, high resolution of soft tissues, and no radiation. It can also locate the lesion accurately and has been widely used in the detection of craniocerebral lesions. So, we hypothesized that there may be cancer- and cancer-related cognitive impairment and then concomitant structural brain abnormalities can be found from T1-weighted MRI.

Our study used T1-weighted MRI to discover the changes in the cerebral cortex structure of cancer patients, and aimed to explore the dynamic changes of brain imaging and cognitive function of lung cancer populations before and after treatment, so as to provide theoretical support for precise intervention and health guidance for patients.

Participants

Patients diagnosed from July to November 2019 with primary lung cancer have been enrolled in a prospective pilot study, everyone has been informed about the purposes and methods of the research at the time of recruitment, and signed informed consent before participation.

Cancer group inclusion criteria are as follows: pathological biopsy diagnosed as lung malignant tumor, without other malignant tumors; no intracranial metastasis or serious cerebrovascular disease; the treatment regimen was platinum-based two-drug combination chemotherapy with or without radiation therapy; right handedness; no symptoms of anxiety and depression as measured by the Hospital Anxiety and Depression Scale (HADs ≤ 8); KPS (Karnofsky Performance Status) ≥ 80; 18 to 70 years old; good comprehension of Chinese language and can complete the neuropsychological assessment scale independently.

Inclusion criteria for healthy controls: health examination confirmed no malignant tumors; HADs ≤ 8; no malignant tumor or serious cerebrovascular disease; 18 to 70 years old; right handedness; good comprehension of Chinese language and can complete the neuropsychological assessment scale independently.

Exclusion criteria: neurological or mental illness; intracranial metastasis, intracranial infiltration, primary brain tumor and severe cerebrovascular disease; have a history of malignancy; history of head trauma and intracranial surgery; HADs༞8; left handedness; there are contraindications for enhanced MRI scanning.

Neuropsychological Assessment

Participants were interviewed by one investigator. Activities of daily living (ADL) is the cancer patient’s quality of life assessment and includes 8 aspects: do housework, take medicine, wash laundry, cook food, shop, use public transportation, make phone calls and handle financial capacity. Each aspect content corresponds to four points, 1-can be completed independently, 2-somewhat difficult, 3-need help, 4-cannot be completed independently at all. The higher the score, the higher the degree of impairment.

The cognitive function of participants were evaluated using the MoCA and Trail Making Test (TMT). Visuospatial and executive function, naming, attention, language, abstraction, delayed memory, and orientation can be examined in MoCA. TMT consists of A and B, TMT-A is widely used to measure psychomotor speed and visual attention, while TMT-B measures cognitive alternation and conversion ability^{25, 26} and is often used to evaluate processing speed, attention and cognitive flexibility.

MRI Scan Acquisition

All brain MRI imaging data were thin-layer scans performed by 3.0T Siemens-Avanto MRI machine with echospeed gradients and standard head coil. Structural images were taken as 3D weighted MRI images, and its parameters were set as TR (repetition time) = 1160ms, TE (echo time) = 4.24ms, TI (inversion time) = 600ms, FOV ( field of view) = 256×256mm², FA (flip angle) = 15°, data matrix = 256×256, voxel size = 1.0×1.0×1.0mm³ .

T1 Image Processing and Analysis

Cortical surface reconstruction and morphological parameters measurement were conducted using Freesurfer software (version 6.0) and processed using MATLAB r2014a and Statistical Parametric Mapping software (SPM12.0). The data of T1 structural MRI images were analyzed based on the surface-based morphometry (SBM). T1-weighted images of individuals were registered into the Talairach standard space, the gray value of the image is standardized in a standard space, remove non-brain tissue such as the skull, and then mark the white matter areas of the brain. According to the position of pons and corpus callosum in standard space, remove the cerebellum and brain stem and divide the brain into left and right hemispheres, and parameterize the triangular meshes of the left and right hemispheres on the surface respectively. Destrieux Atlas template was used to divide brain regions, and the cortical thickness, volume, surface area, curvature and sulcus depth of each brain region were calculated.

Statistical Analysis

All analyses were conducted using SPSS25.0 software. QDEC (Query, Design, Estimate, Contrast) interaction statistics in Freesurfer were used to compare the thickness, volume, surface area, curvature and sulcus depth of brain regions between groups. Differences between groups were corrected by monte Carlo test at P < 0.05 (two pairs). One-way ANOVA was used to evaluate the differences in age between the cancer group at the time of newly diagnosis, after treatment, and the healthy controls. Chi-square test was used to analyze gender, smoking, drinking, educational level, pathological type and clinical classification. Detect the normal distribution, cognitive function in newly diagnosed lung cancer patients and healthy controls was performed using the independent sample t test or the Mann-Whitney U test, cognitive function of D2 group use paired t test or Wilcoxon signed rank test.

A two-sample T test was performed on patients using randomise, a non-parametric testing tool of FSL and TFCE (Threshod Free Cluster Ehancement). P < 0.05 is considered statistical significance. One-way analysis of variance was used to analyze the influence of clinical related factors on the cognition. Calculate the partial correlation coefficient, and analyze the correlation between the ADL, cognitive function tests and the changed brain regions of lung cancer patients.

Patients Characteristics

A total of 51 patients with lung cancer were initially included in the patient group, and 18 were excluded. Among the excluded patients, four images were weird, one cerebral hemorrhage, one cerebral softening, one abnormal data segmentation, and there were 10 scan equipment (scanned by the United Imaging MRI) or sequence errors, and one could not complete the MRI scan due to claustrophobia. Finally, 33 patients with newly diagnosed lung cancer (D1) were included (6 SCLC patients and 27 NSCLC patients). 3 cases of brain metastasis were found during the second craniocerebral MRI acquisition, 5 gave up treatment during treatment, 2 returned to the local hospital for treatment, 2 with renal failure, respiratory failure, KPS < 80 due to deterioration of the disease, 5 refused to follow-up, so there were 16 patients who finally entered the second follow-up (D2), 3 SCLC patients and 13 NSCLC patients (Fig. 1). Lung cancer patients received platinum-based two-drug combination chemotherapy with/without radiotherapy. The healthy controls included 33 cases, including 20 males and 13 females (Table 1).

Table 1

Baseline data and demographic information
Items	Healthy controls(n = 33)	Patient group(n = 49)		t/χ²/F-value	P-value
Items	Healthy controls(n = 33)	D1(n = 33)	D2(n = 16)	t/χ²/F-value	P-value
Age, mean ± SD	55.48 ± 8.22	57.39 ± 6.76	58.38 ± 6.79	0.992^c	0.376^x
Gender (male/female)	20/13	25/8	13/3		0.277^x
Smoking	12(36%)	25(76%)	14(88%)	16.304^b	༜0.01^x
Drinking	17(52%)	21(64%)	8(50%)	1.284^a	0.644^x
Education level					0.558^x
primary/junior /senior/college	10/13/8/2	9/14/5/5	6/7/1/2
Complication					0.658^x
hypertension/diabetes	6/4	4/3	2/0
pathological type					༞0.999^y
SCLC/NSCLC	N/A	6/27	3/13
Clinical classification					0.666^y
Ⅰ/II/III/IV	N/A	3/1/15/14	0/0/10/6
Chemotherapy
PP/TP/EP/GP	N/A	N/A	4/8/3/1/
Radiotherapy(yes/no)	N/A	N/A	16/0
^a t-value, ^b χ²-value, ^c F-value, ^x comparison of three groups of healthy group, newly diagnosed lung cancer patients and treatment group lung cancer patients, ^y comparison between newly diagnosed lung cancer patients and treated lung cancer patients. SD, standard deviation; SCLC, small cell lung cancer;NSCLC, non-small cell lung cancer༛N/A, not applicable; PP, pemetrexed + cisplatin, EP, etoposide + cisplatin, TP, docetaxel + cisplatin, GP, Gemcitabine + cisplatin.

Neuropsychological Assessment

In D1 group, 10 patients (30.3%) showed functional decline of daily life, of which 1 case (3%) showed significant decline. The most commonly affected were walking, personal hygiene (bathing, dressing, combing hair and brushing teeth), housework (laundry, cooking), shopping and transportation. MoCA test showed that delayed recall, abstraction ability, visuospatial and executive ability of newly diagnosed lung cancer patients decreased significantly compared with healthy controls. The duration of the TMT A-B was longer than that of the healthy controls (Table 2). Pathological type, clinical classification, and smoking status did not affect the cognitive function of D1 group (see from supplement material Table S1)

Table 2

The results of activity of daily living and cognitive assessment in newly diagnosed lung cancer group (D1) vs. healthy controls
Cognitive assessment	healthy controls (n = 33)	D1 (n = 33)	t/Z-value	P-value
ADL, mean ± SD	14.21 ± 0.49	15.85 ± 2.59	-3.03^d	༜0.01*
MoCA, mean ± SD
total scores	23.64 ± 3.00	21.18 ± 4.57	2.58^a	0.01*
visual space and executive ability	3.30 ± 1.19	2.36 ± 1.25	-3.13^d	༜0.01*
naming	2.76 ± 0.56	2.48 ± 0.83	-1.47^d	0.14
attention	4.73 ± 1.04	4.67 ± 1.16	-0.03^d	0.97
language	2.70 ± 0.53	2.48 ± 0.83	-0.80^d	0.42
abstraction	1.15 ± 0.87	0.67 ± 0.78	-2.28^d	0.02*
delayed recall	3.18 ± 1.01	2.18 ± 1.04	-3.54^d	༜0.01*
orientation	5.24 ± 0.83	5.45 ± 1.12	-1.84^d	0.07
TMT, mean ± SD
part-A	49.39 ± 12.39	85.88 ± 35.40	-5.24^d	༜0.01*
part-B	57.97 ± 15.80	101.70 ± 49.68	-0.94^d	༜0.01*
^a t-value, ^d Z-value, ^* P values < 0.05 were considered statistical significa

Among the 16 patients with lung cancer (D2) who entered the second follow-up, 11 patients (68.75%) showed an increase in ADL score, indicating poorer daily living ability than before treatment. The results of the MoCA suggested that visual space and executive ability were further weakened, while memory, abstraction, orientation, and attention were not significantly changed. No difference in TMT A-B before and after treatment was found, that is, clinical treatment did not affect the psychomotor speed, visual attention, cognitive alternation and conversion ability of lung cancer patients (Table 3). The results suggested that the clinical stage, pathological type, and treatment protocol did not affect the ADL, visual space and executive ability of the patients in the D2 group. Univariate analysis results were listed in supplement material Table S2.

Table 3

Evaluation results of activity of daily living and cognitive function of D2 group before and after treatment
Cognitive assessment	D2 group		t/Z value	d-value	P-value
Cognitive assessment	Pre-treatment	Post-treatment	t/Z value	d-value	P-value
ADL(scores)	16.38 ± 2.78	18.31 ± 2.77	2.93^a	0.78	0.01*
MoCA(scores)
total scores	21.75 ± 3.77	20.00 ± 4.72	−1.23^d		0.22
visual space and executive ability	2.56 ± 1.32	1.75 ± 1.34	2.66^a	0.66	0.02*
naming	2.56 ± 0.81	1.94 ± 1.24	2.08^a	0.52	0.06
attention	5.13 ± 0.72	4.56 ± 1.63	−1.23^a	0.31	0.27
language	2.31 ± 0.87	2.31 ± 1.01	༜0.01^d		༜0.99
abstraction	0.69 ± 0.79	0.81 ± 0.91	0.38^a	0.10	0.71
delayed recall	2.06 ± 1.00	1.75 ± 1.24	1.10^a	0.28	0.29
orientation	5.50 ± 0.82	5.75 ± 0.58	−1.41^d		0.16
TMT(second)
part-A	76.69 ± 30.12	87.94 ± 33.76	1.32^a	0.33	0.21
part-B	87.62 ± 31.38	94.06 ± 31.81	−0.63^d		0.53
^d effect size.

Imaging Analyses

Gender, age, smoking and drinking were taken as covariables in the calculation of cortical changes and partial correlation analysis.

The thickness and volume of cerebral cortex in the D1 group were significantly lower than those in the healthy controls. Cortical thickness decreased mainly in the bilateral superior temporal gyrus and rostral middle frontal cortex, left anterior central gyrus, right posterior central gyrus, and right inferior parietal gyrus (Fig. 2 and Table 4). The brain region with smaller cortical volume was the left temporal lobe, especially the temporal pole and middle temporal gyrus of the left brain. There were no significant differences in cortical surface area, curvature and sulcus depth between the D1 group and the healthy controls.

Table 4

List of brain regions with changes in cerebral cortex between D1 group vs. healthy controls
Items	Index	Brain region	Cluster size(mm²)	Vertex sequence	Peak Talairach Coordinates			P-value
Items	Index	Brain region	Cluster size(mm²)	Vertex sequence	x	y	z	P-value
Thickness	C1	STG_L, STG_R	8667.04 8106.55	14516 14049	-53.1 65.2	-24.0 -17.0	-4.0 3.0	0.0001 0.0001
	C2	rMFC_L, rMFC_R	1496.92 2344.17	2060 3625	-38.1 27.7	50.0 57.8	-3.4 -9.5	0.0016 0.0001
	C3	ACG_L	3215.42	7095	-52.5	-6.6	38.5	0.0001
	C4	IPG_R, PCG_R	1304.28 1318.63	2442 3210	34.0 62.1	-71.1 -9.6	28.7 28.9	0.0035 0.0032
Volume	C5	TP_L	1937.13	2931	-28.2	5.80	-34.2	0.0001
	C6	MTG_L	932.02	1530	-58.1	-38.6	-14.7	0.0439
STG, superior temporal gyrus; rMFC, rostral middle frontal cortex; ACG, anterior central gyrus; IPG, inferior parietal gyrus; PCG, posterior central gyrus. TP, temporal pole; MTG, middle temporal gyrus. L, left; R, right.

After 2–4 months of treatment, the thickness of right rostral middle frontal cortex in the D2 group patients was thinner than before treatment (Fig. 3 and Table 5). No significant statistical changes were observed in volume, surface area, curvature and sulcus depth.

Table 5

List of brain regions with changes in cortical thickness in patients with lung cancer in treatment group
Group	Index	Brain region	Cluster size(mm²)	Vertex sequence	Peak Talairach Coordinates			P-value
Group	Index	Brain region	Cluster size(mm²)	Vertex sequence	x	y	z	P-value
Pre-treatment vs. Post-treatment	C7	rMFC_R	3023.39	4486	38.7	41.0	24.0	0.0001

Correlation Analysis

Taking gender, age, smoking and drinking as covariables, in newly diagnosed cancer group (D1), the brain regions with decreased thickness were significantly negatively correlated with TMT-A, including left superior temporal gyrus, bilateral rostral middle frontal cortex, left anterior central gyrus, and right posterior central gyrus. The reduced volume of the left temporal pole was positively correlated with naming (r = 0.39, P = 0.03) and language ability (r = 0.43, P = 0.02), while the decreased volume of the left middle temporal gyrus was significantly positively correlated with attention (r = 0.39, P = 0.03) and orientation (r = 0.39, P = 0.04), as shown in Table 6.

Table 6

Partial correlation analysis results of cerebral cortex structure changes and cognitive function in patients with newly diagnosed lung cancer
Index	Brain region	Cognitive function	r-value	P-value
Thickness	STG_L	TMT-A	-0.42	0.02
	rMFC_L	TMT-A	-0.43	0.02
	rMFC_R	TMT-A	-0.48	༜0.01
	ACG_L	TMT-A	-0.49	༜0.01
	PCG_R	TMT-A	-0.39	0.04
	IPG_R	TMT-A	-0.38	0.04
Volume	TP_L	Naming	0.39	0.03
	TP_L	Language	0.43	0.02
	MTG_L	Attention	0.39	0.03
	MTG_L	Orientation	0.39	0.04
“r” is correlation coefficient.

Our results illustrated that the D1 group exhibited cognitive impairment in delayed recall, abstraction, visuospatial and executive ability, psychomotor speed, cognitive alternation and conversion ability with widespread cerebral cortex atrophy. Additionally, the D2 group exhibited cognitive deficits shortly after chemotherapy and/or radiotherapy, especially in visuospatial and executive ability together with thinner thickness in right rostral middle frontal cortex. At the same time, partial correlation analysis showed that some cognitive impairments are related to changes in the cerebral cortex.

Differences of neuropsychological assessment

ADL scale results revealed that about one-third of patients with lung cancer had impaired activities of daily living prior to treatment, about two thirds of patients demonstrating a worsening of functional status after treatment. Decoster L et al. did find that 63% older patients with lung cancer experienced a decrease in the activities of daily living, and functional decline is observed in almost half of the patients during treatment. In multivariable analysis, radiotherapy was predictive for ADL decline, and baseline performance status were predictive for overall survival²⁷. Meanwhile, ADL demonstrated acceptable internal consistency (Cronbach's alpha generally between 0.70 and 0.90) and test-retest reliability among patients with lung cancer, and were consistent with clinical worsening following diagnosis or hospitalization²⁸. Our findings suggested the demand for early intervention in patients with lung cancer to reduce the progression of cachexia, improve functional prognosis, alleviate the burden of medical resources, and improve quality of life.

Regarding neuropsychological assessment, the MoCA results showed that the delayed recall, abstraction, visuospatial and executive abilitiy in the D1 group patients were worse relative to healthy controls, and the duration of TMT A-B was also different, suggesting that the psychomotor speed, cognitive alternation and conversion ability were worse. And following treatment, the D2 group performed worse than before, with special emphasis in visuospatial and executive ability. This finding is consistent with the subjective complaints of patients in clinical diagnosis and treatment. Considering the post-traumatic stress of cancer patients after being aware of the condition may affect cognition, this study has preliminarily excluded patients with anxiety and depression when they were recruited. Therefore, it can be considered that the cognitive impairment of lung cancer patients before and after treatment is only caused by the cancer and the cancer treatment.

After treatment, visuospatial and executive ability deteriorated in the D2 group, these cognitive deficits were similar to those previously described¹⁶. Subjective cognitive decline up to 11% in NSCLC patients receiving chemotherapy after 2–4 months, with recovery after 4–6 months. Meanwhile, objective measurement of attention showed improvement over the course of therapy²⁹, but the cognitive domains such as memory and abstraction ability were uncertain. The possible reason for the lack of change in memory and abstraction ability after treatment was that the follow-up time of this study was relatively short, and the second follow-up started after recieving 2–4 months of treatment, the follow-up time is not fixed, the patients' memory and abstraction ability might not yet be affected by treatment, or treatment does not affect the subjects’ memory and abstraction ability. Therefore, visuospatial and executive ability of lung cancer patients were deteriorated after treatment in this study, confirming that clinical treatment can aggravate cognitive dysfunction.

Differences of cerebral cortex structure changes

The main changes in the brain region were concentrated in the left brain in this study, One of the reasons might be related to the fact that the participants in this study were all right-handed. Another reason is that the underlying cause of the priority vulnerability of the left brain might be related to the asymmetry of hemodynamics and developmental trajectories³⁰. Most relevant studies have confirmed that the changes in the cerebral cortex caused by cancer and cancer treatment were mainly concentrated in the frontal, temporal and parietal lobes^{31, 32}. Lung cancer patients exhibited verbal memory deficits together with a widespread white matter damage before the treatment, following treatment, the patients performed worse visuospatial and verbal fluency ability, as well as structural gray matter and white matter differences in bilateral regions integrating the paralimbic system¹⁶, at the same time, attention, executive function and memory were affected, leading to confusion and decreased concentration³³. Structure determines function, the results of this study indicated that the thickness and volume of the frontal, temporal, and parietal cortex were atrophied, suggesting that lung cancer patients would not only experience structural changes in the cerebral cortex, but also emotional changes and cognitive dysfunctions.

The correlation between cerebral cortex and cognition

The TMT-A is mainly used to evaluate the processing speed³⁴, the higher the TMT-A test score, the worse the processing speed. Partial correlation analysis showed the thickness decreased in the superior temporal gyrus, rostral middle frontal cortex, the anterior central gyrus, the posterior central gyrus, and the superior parietal gyrus were significantly negatively correlated with TMT-A, indicating that the smaller the thickness of the above-mentioned brain reagions, the longer TMT-A will take, and the worse the processing speed will be. The volume of temporal pole is positively correlated with naming and language, and the middle temporal gyrus is positively correlated with attention and orientation, indicating that the smaller the volume of the temporal pole and middle temporal gyrus, the worse the patients’ naming, language, attention, and orientation. Cognitive changes related to cancer or cancer treatment have been widely recognized, and studies have reported that cognitive impairment is associated with brain atrophy and white matter changes^{35, 36}, this is consistent with our findings, but the specific pathogenesis of these neurocognitive changes remains unclear.

There are several deficiencies in this study. First, there is a high rate of loss to follow-up, only a small number of patients taking the second MRI acquision, we cannot performed a stratify analysis of tumor clinical classification on patients' cognition. Besides, our work confirmed the effects of cancer and cancer treatment on cerebral cortex and cognition in lung cancer patients, but the specific mechanisms remain unclear. In the future, we will conduct long-term follow-up of brain MRI and cognitive function for these patients, and expand the sample size of the patient group and the healthy controls to improve the experimental rigor and reliability.

In conclusion, our research showed that lung cancer and clinical treatment can cause cerebral cortex structure changes and cognitive impairment, and there is a correlation between the two, comforming the real existence of CRCI.

Acknowledgments

We would like to thank Jing Ren, Min Wang and Heping Deng for technical assistance during the magnetic resonance acquisitions. We thank all authorship for their contribution to the study. Meanwhile, we should thank all participants for their collaboration.

Consent to Participate

Every participaint signed informed consent before participation.

Consent to Publish

The Author confirms: that the work described has not been published before (except in the form ofan abstract or as part of a published lecture，review，or thesis), that it is not under consideration for publication elsewhere, that its publication has been approved by all co-authors, that its publication has been approved (tacitly or explicitly) by theresponsible authorities at the institution where the work is carried out.

Compliance with Ethical Standards

This study was approved by the Ethics Committee of Sichuan Cancer Hospital (No. IIT2021087). and all methods were carried out in accordance with the Declaration of Helsinki.

Author Contributions

CW, WDW: study design. CW: draft the manuscript. CW, YL, MQG: statistical analysis. CW: neuropsychological assessment. XL, LPL, ZYF: images collection. ZFW, KZL, MY, YRC: clinical data collection. LD, WDW: manuscript modification and enrichment. All authors: approval of final version to be published and agreement to be accountable for the integrity and accuracy of all aspects of the work.

Conflict of Interest

The author(s) indicated no potential conflicts of interest.

Funding Sources

This study was supported grants from Ministry of Science and Technology of the People’s Republic China (N0. 2017YFC0113904), Department of Science and Technology of Sichuan Province (NO. 2017SZ0004) and Science and Technology Bereau of Chengdu (N0. 2021YF0501659SN)

Availability of Data and Material

The datasets used or analysed during the current study are available from the corresponding author on reasonable request.

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No competing interests reported.

Cerebral Cortex Structure Changes And Their Correlation With Cognitive Function In Lung Cancer Patients

Status:

Version 1

Abstract

Figures

1 Introduction

2 Patients And Methods

3 Results

4 Discussion

5 Limitation

6 Conclusions

7 Statements And Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1